FAMP, a novel apoA-I mimetic peptide, suppresses aortic plaque formation through promotion of biological HDL function in ApoE-deficient mice.
FAMP, a novel apoA-I mimetic peptide, suppresses aortic plaque formation through promotion of biological HDL function in ApoE-deficient mice.
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DOI：
10.1161/jaha.113.000048
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发表时间：
2013-05-24
影响因子：
5.4
通讯作者：
Saku K
中科院分区：
文献类型：
--
作者：
Uehara Y;Ando S;Yahiro E;Oniki K;Ayaori M;Abe S;Kawachi E;Zhang B;Shioi S;Tanigawa H;Imaizumi S;Miura S;Saku K
载脂蛋白（apo） A‐I是一种主要的高密度脂蛋白（HDL）蛋白，它通过ATP结合盒转运蛋白A1 （ABCA1）导致胆固醇从外周细胞流出，从而产生HDL并逆转巨噬细胞泡沫细胞表型。Pre - β1 HDL是HDL的最小亚部分，被认为代表了新形成的HDL，它是最活跃的游离胆固醇受体。此外，它还可能对心血管疾病（CVD）具有保护作用。我们开发了一种新的不含磷脂的apoA‐I模拟肽（Fukuoka University apoA‐I mimetic peptide， FAMP）。FAMP5型（FAMP5）在体外对A172细胞、小鼠和人巨噬细胞的胆固醇具有较高的外排能力，其外排主要依赖于ABCA1转运体。FAMP5与人HDL或全血浆孵育产生小HDL颗粒，琼脂糖凝胶电泳上带电的富含apoA‐I的颗粒作为前β HDL迁移。在高脂饮食喂养的apoE -缺陷小鼠中，FAMP5治疗16周后显著抑制了主动脉斑块形成（紊乱的FAMP为31.3±8.9%，而高剂量FAMP5为16.2±5.0%，P<0.01）和血浆C反应蛋白和单核细胞化学吸引蛋白- 1。此外，它还显著增强了小鼠高密度脂蛋白介导的胆固醇外排能力。一种新开发的apoA‐I模拟肽，FAMP，通过增强HDL的生物学功能具有抗动脉粥样硬化作用。FAMP可能具有显著的动脉粥样硬化保护潜力，并被证明是一种新的治疗CVD的工具。
Apolipoprotein (apo) A‐I is a major high‐density lipoprotein (HDL) protein that causes cholesterol efflux from peripheral cells through the ATP‐binding cassette transporter A1 (ABCA1), thus generating HDL and reversing the macrophage foam cell phenotype. Pre‐β1 HDL is the smallest subfraction of HDL, which is believed to represent newly formed HDL, and it is the most active acceptor of free cholesterol. Furthermore it has a possible protective function against cardiovascular disease (CVD). We developed a novel apoA‐I mimetic peptide without phospholipids (Fukuoka University ApoA‐I Mimetic Peptide, FAMP). FAMP type 5 (FAMP5) had a high capacity for cholesterol efflux from A172 cells and mouse and human macrophages in vitro, and the efflux was mainly dependent on ABCA1 transporter. Incubation of FAMP5 with human HDL or whole plasma generated small HDL particles, and charged apoA‐I‐rich particles migrated as pre‐β HDL on agarose gel electrophoresis. Sixteen weeks of treatment with FAMP5 significantly suppressed aortic plaque formation (scrambled FAMP, 31.3±8.9% versus high‐dose FAMP5, 16.2±5.0%; P<0.01) and plasma C‐reactive protein and monocyte chemoattractant protein‐1 in apoE‐deficient mice fed a high‐fat diet. In addition, it significantly enhanced HDL‐mediated cholesterol efflux capacity from the mice. A newly developed apoA‐I mimetic peptide, FAMP, has an antiatherosclerotic effect through the enhancement of the biological function of HDL. FAMP may have significant atheroprotective potential and prove to be a new therapeutic tool for CVD.